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Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA

M Nakanishi1, G R Adami, R S Robetorye

  • 1Roy M. and Phyllis Gough Huffington Center on Aging, Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 9, 1995
PubMed

Insights

p21Sdi1 protein inhibits cell cycle progression in G0 and early G1 phases. Decreased p21Sdi1 expression is necessary for DNA synthesis and entry into mitosis, promoting cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • p21Sdi1 (also known as Cip1 and Waf1) is a known inhibitor of DNA synthesis.
  • It inhibits G1 cyclin-dependent kinases (Cdks) and interacts with proliferating cell nuclear antigen.
  • p21Sdi1 is transcriptionally regulated by wild-type p53.

Purpose of the Study:

  • To analyze the role of p21Sdi1 in normal human fibroblast cells arrested in G0.
  • To investigate the necessity of p21Sdi1 downregulation for cell cycle progression.

Main Methods:

  • Analysis of p21Sdi1 levels in G0-arrested vs. mitogen-stimulated fibroblasts.
  • Immunodepletion of cyclins and Cdks.
  • Expression of antisense p21Sdi1 RNA in G0-arrested cells.

Main Results:

  • An excess of p21Sdi1 was observed in G0-arrested cells compared to early S phase cells.
  • Antisense p21Sdi1 RNA expression induced DNA synthesis and mitosis in G0-arrested cells.

Conclusions:

  • p21Sdi1 functions in the G0 and early G1 phases of the cell cycle.
  • Downregulation of p21Sdi1 gene expression is essential for initiating DNA synthesis and cell cycle progression.

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